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Abstract: Indexation of regulatory T cells (Treg) to the number of activated T cells constitutes a homeostatic mechanism ensuring that T-cell expansion remains under control. However, immune hyperactivation observed in HIV-infected patients suggests a possible dysfunction of this mechanism. Here we show that the Treg/IL-2–producing cells' balance is deeply disturbed in viremic HIV-infected patients. We found a lower expression of IL-2 receptor alpha on Treg from viremic patients. We confirmed in vitro that HIV infection of Treg downregulates IL-2 receptor alpha and phosphorylated STAT5. Our results argue for an impaired capacity of Treg to sense the expansion of activated T cells in HIV-infected patients that could contribute to the immune deregulation.

All the authors declare that they do not have a commercial or other association that might pose a conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Supported by a grant from Fondo de Investigación Sanitaria (FIS PS09/02618, FIS PI12/00934, FIS PS09/02523, FIS PI12/01763, and P11/02014); INTRASALUD PI09/02029; Spanish AIDS Research Network of Excellence (RIS) (RD12/0017/0037 and RD12/0017/0029); from the Ministerio de Sanidad, Política Social e Igualdad (grant EC11-520); Fundación Progreso y Salud (grant PI-0081-2011); and from Consortium INDISNET S-2011-BMD2332 (CM). M.P. is supported by the “Ramon y Cajal” program of Ministerio de Ciencia e Innovación (RYC-2009-05486). R.C.-R. (CP07/00117) and Y.M.P. (CP07/00240) are supported by the Fondo de Investigación Sanitaria through the “Miguel Servet” program. Y.M.P. is also supported by the Consejeria de Salud y Bienestar Social of Junta de Andalucia (“Nicolas Monardes” program C-0010/13).

G.M.-L. and D.J.-R. contributed equally to this work. G.M.-L. and D.J.-R. performed research, analyzed data, and contributed to the preparation of the manuscript. M.P. produced the HIV and performed in vitro research. M.A.M.-F. and M.L. contributed to the design of the project and the preparation of the manuscript. Y.M.P. and R.C.-R. were responsible for the overall study, designed the project, and wrote the manuscript. Y.M.P. and R.C-R. contributed equally to this work.